Role of masseter muscle β₂-adrenergic signaling in regulation of muscle activity, myosin heavy chain transition, and hypertrophy.

Abstract

Chronic administration of clenbuterol (CB), a lipophilic β₂-adrenoceptor (β₂-AR) agonist, induces skeletal muscle hypertrophy and slow-to-fast fiber-type transitions in mammalian species, but the mechanism and pathophysiological roles of these changes have not been explored. Here, we examined the effects of CB not only on masseter muscle mass, fiber diameter, and myosin heavy chain (MHC) composition, but also on daily muscle activity, a factor influencing muscle phenotype, by means of electromyogram analysis in rats. MHC transition towards faster isoforms was induced by 2-week CB treatment. In addition, daily duty time was increased at 1 day, 1 week, and 2 weeks after the start of CB treatment and its increase was greater at high activity level (6-fold) than at low activity level (2-fold). In order to examine whether these effects of CB were mediated through muscle or CNS β₂-AR stimulation, we compared these effects of CB with those of salbutamol (SB), a hydrophilic β₂-AR agonist. SB treatment induced masseter hypertrophy and MHC transition, like CB, but did not increase daily activity. These results suggest that CB-mediated slow-to-fast MHC transition with hypertrophy was induced through direct muscle β₂-AR stimulation, but the increase of daily duty time was mediated through the CNS.

• Authors: Yoshiki Ohnuki, Daisuke Umeki, Wenqian Cai, Nobuhiko Kawai, Yasumasa Mototani, Kouichi Shiozawa, Hui-Ling Jin, Takayuki Fujita, Eiji Tanaka, Yasutake Saeki, Satoshi Okumura
• Journal: Journal of pharmacological sciences (J Pharmacol Sci) Vol. 123 Issue 1 Pg. 36-46 (Sep 20 2013) ISSN: 1347-8648 [Electronic] Japan
• PMID: 23985574 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adrenergic beta-2 Receptor Agonists
• Receptors, Adrenergic, beta-2
• Myosin Heavy Chains
• Albuterol
• Clenbuterol

Topics

• Adrenergic beta-2 Receptor Agonists (pharmacology)
• Albuterol (pharmacology)
• Animals
• Central Nervous System (drug effects, physiology)
• Clenbuterol (pharmacology)
• Electromyography (drug effects)
• Hypertrophy
• Masseter Muscle (drug effects, metabolism, pathology, physiology)
• Myosin Heavy Chains (metabolism)
• Rats
• Receptors, Adrenergic, beta-2 (drug effects, physiology)
• Signal Transduction (drug effects, physiology)